Hepatitis C virus‐specific immune responses following direct‐acting antivirals administered during recent hepatitis C virus infection

Abstract

Individuals who spontaneously clear hepatitis C virus (HCV) infection have demonstrated evidence of partial protective immunity, whereas treatment-induced clearance provides little or no protection against reinfection. We aimed to investigate whether treatment of acute HCV infection with direct-acting antivirals (DAA) prevents establishment of, or reverses, T-cell exhaustion, leading to a virus-specific T-cell immune profile more similar to that seen in spontaneous clearance. The magnitude and breadth of HCV-specific T-cell responses before and after DAA or interferonbased therapy in acute or chronic HCV were compared to those of participants with spontaneous clearance of infection, using Enzyme-linked Immunospot (ELISPOT).PBMCs were available for 55 patients comprising 4 groups: spontaneous clearance (n = 17), acute interferon (n = 14), acute DAA (n = 13) and chronic DAA (n = 11). After controlling for sex, the magnitude of post-treatment HCV-specific responses after acute DAA treatment was greater than after chronic DAA or acute IFN treatment and similar to those found in spontaneous clearers. However, spontaneous clearers responded to more HCV peptide pools indicating greater breadth of response. In conclusion, early treatment with DAAs may prevent or reverse some degree of immune exhaustion and result in stronger HCV-specific responses post-treatment. However, individuals with spontaneous clearance had broader HCV-specific responses.

Hepatitis C Virus and the Host: A Mutual Endurance Leaving Indelible Scars in the Host’s Immunity

“…However, one study found that only a partial restoration of immune responses could be obtained in HCV patients treated with DAAs, with increased proliferation of HCV-specific CD4 and CD8 T cells, accompanied by an impaired ability to secrete IFNγ and IL2 [ 101 ]. Also, a recent study highlighted the importance of early DAA treatment commencement during the acute phase of HCV infection, which led to a reduction in immune exhaustion and to stronger HCV-specific T cell responses after treatment, thus reducing the risk of possible reinfection [ 102 ].…”